The hypothesis underlying the proposed project is that nerve growth factor (NGF) or other neuronotrophic factors act as mediators by which dental tissues regulate the development and remodeling of their innervation. The dentition of most mammals, including humans, undergoes a complete postnatal turnover accompanied by degeneration of nerve terminals in the primary teeth and development of an innervation to a new and expanded set of permanent teeth. The mechanisms regulating the radical remodeling of dental innervation have not been explored, but it is certain that the dental tissues themselves exert an influence. In recent years it has become evident that development and maintenance of peripheral neurons are modulated by signal molecules (neuronotrophic factors) produced by their target organs. The most fully characterized of these factors is NGF which acts on sympathetic and sensory ganglion neurons. The specific aims of the proposed studies are (1) to determine whether feline dental pulp contains NGF or other neuronotrophic factors, (2) to determine the developmental time course of production of these agents by the pulp, and (3) to determine whether the pulp responds to denervation by increasing production of NGF or other neuronotrophic factors. Samples of canine pulp tissue will be obtained from cats at all stages of dental development and from cats in which teeth have been surgically denervated. NGF content in extracts of pulp tissue samples will be assessed by a two-site radioimmunoassay and a specific in vitro bioassay. Screening for other neuronotrophic factors will involve testing a variety of neuron types in culture for survival and growth responses to extracts and explants of pulp tissue. These studies will provide information essential for more extensive investigations of trophic signals from dental tissues to the neurons inner-vating them. If evidence for a role of NGF is obtained, subsequent experiments will address the questions of its specific cellular source and its essentiality in development and regeneration of the dental innervation. If other neuronotrophic factors appear to be important, their molecular characteristics will be investigated.